To the Editor: Dr Singh and colleagues1 conducted a meta-analysis of the relationship between inhaled anticholinergic medications and major cardiovascular adverse events. This study's findings were contrary to results from a previously published meta-analysis.2 The study by Singh et al relied on information obtained from medical journals, Web sites of pharmaceutical companies, and regulatory authorities. Publications of clinical trials are summary reports that by necessity omit many details. Infrequent adverse events are often not reported because the small number observed in a single trial is not informative. The study by Singh et al identified 58 cases of major cardiovascular events from 8 published reports of 11 placebo-controlled tiotropium trials (excluding the 2000 study by Casaburi et al3 and the study by Donohue et al,4 which resulted in double counting of patients by Singh et al). Even if all trials are published, meta-analyses of published reports remain vulnerable to unreported cases.
Kesten S, Leimer I, Jara M. Risk of Major Adverse Cardiovascular Events With Inhaled Anticholinergics in Patients With Chronic Obstructive Pulmonary Disease. JAMA. 2009;301(12):1223-1226. doi:10.1001/jama.2008.949